Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo

Hiroyuki Shibata, Hiroyuki Yamakoshi, Atsuko Sato, Hisatsugu Ohori, Yuichi Kakudo, Chieko Kudo, Yayoi Takahashi, Mika Watanabe, Hiroshi Takano, Chikashi Ishioka, Tetsuo Noda, Yoshiharu Iwabuchi

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Curcumin (diferuloylmethane) has chemopreventive and chemotherapeutic potentials against various types of cancers. We have developed a series of curcumin analogs to improve its low bioavailability by enhancing its potentials. The newly synthesized analog GO-Y030 [(1E, 4E)-1,5-bis-(3,5(-bismethoxymethoxyphenyl) penta-1,4-dien-3-one]showed a 30-fold greater growth suppression in vitro via similar molecular mechanisms to curcumin. The availability of this analog was examined by using a mouse model harboring the germ-line mutation of Apc, Apc580D/+, in vivo. Apc580D/+ mice had a very limited survival time with an intestinal obstruction due to polyposis. The average tumor number in mice fed GO-Y030 was reduced to 61.2% of those that were fed the basal diet (P < 0.05). Compared with Apc580D/+ mice fed the basal diet (median survival time = 166.5 days), a significantly prolonged lifespan (213 days) was observed in Apc580D/+ mice fed GO-Y030. The chemopreventive effect with GO-Y030 was improved, compared with curcumin (191 days). The survival benefit corresponded to the diminished intestinal tumor incidence in Apc580D/+ mice fed GO-Y030. No adverse reactions were observed, judging from body weight or biochemical data concerning liver and renal damage. Degradation of accumulated β-catenin with curcumin is one of the major mechanisms of chemoprevention in colorectal carcinogenesis. It was demonstrated that the number of β-catenin-positive adenoma cells in Apc580D/+ mice fed GO-Y030 was reduced.

Original languageEnglish
Pages (from-to)956-960
Number of pages5
JournalCancer science
Volume100
Issue number5
DOIs
Publication statusPublished - 2009 Apr 30

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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